Can Wallabies Replace the Lab Rat?

Barehanded, neurobiologist Craig Zaidman reaches into the pouch of a female tammar wallaby. At his touch, this squirming, 18-inch high cousin of the kangaroo becomes as docile as a milk-cow; possibly because the hand feels like a young "joey" crawling into the pouch. After Zaidman separates the pouch entrance from the surrounding grey-brown fur, he plucks out a hairless, finger-length "pouch-young" from a teat; it comes away from the nipple like a grape off a vine.

"This is what makes wallabies so great for study. It takes virtually no effort to hold what is essentially an embryo in the palm of my hand," says Zaidman, a visiting Fulbright scholar to the Australian National University Research School of Biological Sciences in Canberra. "This one can be returned to the pouch, alive and well, for further monitoring," he adds, before weighing the rugged, 55-day-old for his inquiry into how the developing eyeball makes connections with the brain.

Neurobiological researchers who use more traditional lab animals only dream of such easy access. Most of the brain's "hard-wiring" occurs early in embryonic development, when access is difficult. By the time the young of popular lab animals such as rats or cats are available, their brains are already past the crucial stage when the onset of visual activity occurs.

Because of this obstacle, researchers are usually forced to dissect dead specimens, examine cells in petri dishes, or study such non-mammals as frogs. Some neurobiologists in Italy were able to make electrical recordings of embryonic brain activity in live rats, but the effort proved so difficult that no one has yet repeated the feat, Zaidman says. But by studying the wallaby (Macropus eugenii), scientists can make recordings in a live, intact animal well before visual activity begins, says Richard Mark, founder of the ANU's program.

Like all marsupials, wallabies are mammals; they have hair, produce milk and are warm-blooded. But unlike the rest of the mammal class, marsupials do not nourish their young in a placenta from conception to delivery. Instead, their partially-developed young spend only 28 days in the womb before crawling, slug-like, to the marsupium, or pouch, outside the mother's body. There they take another 180 days to suckle, differentiate and grow into fully-formed joeys.

Meanwhile, these developing pouch-young are basically free-living, readily accessible fetuses. Neither surgery nor anesthesia is required to get them, which eliminates a potential source of error.

An additional bonus is that maturation happens slowly inside the pouch; a developmental activity that takes 24 hours in rats takes three weeks in a wallaby. The drawn-out pace means that sequential events can be viewed distinctly in the embryonic brain: for instance, optic axons can be easily tracked as they extend from the back of the eyeball into the
superior colliculus -- the portion of the brain controlling eye movement.

But for Mark and his team to even make such studies, they first had to establish a colony. "You can't just call up a biological supply house and say 'I'd like100 wallabies,'" points out Dr. Peter Janssens, co-author of The Developing Marsupial: Models for Biomedical Research. He adds that a lot of work had to be done on simple care and feeding, as well as on the applicability of wallabies to other mammals."It took 15 years of background work before we could even get
results," Mark adds.

Simply collecting the first animals was an adventure. The team had to improvise tools to capture the fast-hopping wallabies from an island off South Australia, where their numbers had become unnaturally high. The first nets often snapped from the force of the speeding marsupials. (They now use modified, oversized butterfly nets.)

There was also the obstacle of overcoming the bias against the use of marsupials as lab animals. Early 19th-century taxonomists had thought Australian marsupials were a more primitive subcategory of mammals, since they lacked a corpus callosum -- the brain formation that enables the two hemispheres to communicate. It took decades before scientists discovered that marsupials did indeed have an equivalent structure, called the fasciculus aberrans. "Contrary to early taxonomists, wallabies are not second-class mammals," Mark says, adding that "it's not the differences between wallabies and other mammals that make wallabies so interesting as a research model; it's the things that make them the same."

Wallaby studies have already paid dividends: by using these animals, Mark and his team found that optic axons don't randomly form connections with the superior colliculus, as previously thought. Instead, axons target specific spots. Other workers in several research centers throughout Australia now use marsupials as lab animals, and in the U.S. the wallaby's South American cousin Monodelphis domestica (the gray, short-tailed opossum) has occasionally been imported for study.

University of Melbourne's Marilyn Renfree, who has spent 30 years studying wallaby reproduction and development, sees this interest as long overdue. "But then I'm a marsupial chauvinist," she says.

-- Dan Drollette Jr. in Canberra, Australia
Scientific American

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